Our study aimed at finding a mechanistic relationship between the gut microbiome and breast cancer. Breast cancer cells are not in direct contact with these microbes, but disease could be influenced by bacterial metabolites including secondary bile acids that are exclusively synthesized by the microbiome and known to enter the human circulation. In murine and bench experiments, a secondary bile acid, lithocholic acid (LCA) in concentrations corresponding to its tissue reference concentrations (< 1 μM), reduced cancer cell proliferation (by 10-20%) and VEGF production (by 37%), aggressiveness and metastatic potential of primary tumors through inducing mesenchymal-to-epithelial transition, increased antitumor immune response, OXPHOS and the TCA cycle. Part of these effects was due to activation of TGR5 by LCA. Early stage breast cancer patients, versus control women, had reduced serum LCA levels, reduced chenodeoxycholic acid to LCA ratio, and reduced abundance of the baiH (7α/β-hydroxysteroid dehydroxylase, the key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial generation of LCA in early breast cancer.

Abstract:The absolute number of membrane-

An extensive search for the cell membrane targets for lipopolysaccharide (LPS), the major causative agent of Gram-negative septic shock, resulted in the identification of CD14 as the major endotoxin 'receptor'. Besides recognition of LPS, several new aspects of its biological functions have been described recently. In this review the different CD14 forms, their most important biological and biochemical features, signalling properties, cellular and subcellular distribution and association with different diseases are discussed in detail, showing that these molecules posses several unique biological functions and further proving their central role in innate immunity.